Pyrithioxin dihydrochloride (Pyritinol dihydrochloride)

Combined mutagenesis and metabolic regulation to enhance D-arabitol production from Candida parapsilosis

D-Arabitol is an important pentitol that is widely used in the food, pharmaceutical and chemical industries. It is mainly produced by yeasts during the biotransformation of glucose. To obtain strains with high D-arabitol production, Candida parapsilosis was mutated using atmospheric and room temperature plasma (ARTP). Among the screened mutants, mutant A6 had the highest yield at 32.92 g/L, a 53.98% increase compared with the original strain (21.38 g/L). Furthermore, metabolic regulators were added to the medium to improve D-arabitol production. Pyrithioxin dihydrochloride increased D-arabitol production by 34.4% by regulating glucose-6-phosphate dehydrogenase, and 4-methylpyrazole increased D-arabitol production by 77.4% compared with the control group by inhibiting alcohol dehydrogenase activity. Amphotericin B and Triton X-100 increased D-arabitol production by 23.8% and 42.2% by improving the membrane permeability and dissolved oxygen content, respectively. This study may provide important implications for obtaining high-yield D-arabitol strains.

Stability-indicating chemometric methods for the determination of pyritinol dihydrochloride

Three multivariate calibration methods, including classical least square with nonzero intercept (CLS), principal component regression (PCR) and partial least square (PLS), have been used for the determination of pyritinol dihydrochloride in the presence of its degradation product. The CLS, PCR and PLS techniques are useful in spectral analysis because the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry has greatly improved the precision and predictive abilities of these multivariate calibrations. A training set was constructed for the mixture and the best model was used for the prediction of the concentration of the selected drug. The proposed procedures were applied successfully in the determination of pyritinol dihydrochloride in laboratory-prepared mixtures and in commercial preparations. Pyritinol dihydrochloride was analysed with mean accuracies 99.99 +/- 0.905, 99.91 +/- 0.966 and 99.92 +/- 0.962 using the CLS, PCR and PLS methods respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed procedures were found to be rapid and simple and required no preliminary separation. They can therefore be used for the routine analysis of pyritinol dihydrochloride in quality-control laboratories.

Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID)

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

Stability-indicating methods for determination of pyritinol dihydrochloride in the presence of its precursor and degradation product by derivative spectrophotometry

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvent. Linear relationships were obtained in the ranges of 6-22 microg/mL for the (1D) method and 6-20 microg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 +/- 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 +/- 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of < or = 10% (II) and < or = 50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.

Stability-indicating electrochemical methods for the determination of meclophenoxate hydrochloride and pyritinol dihydrochloride using ion-selective membrane electrodes

The construction and electrochemical response characteristics of polyvinyl chloride (PVC) membrane sensors for the determination of meclophenoxate hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their degradation products are described. The sensors are based on the use of the ion-association complexes of (I) and (II) cation with sodium tetraphenyl borate and ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In addition beta-cyclodextrin (beta-CD) membranes were used in the determination of I and II. These ion pairs and beta-CD were then incorporated as electroactive species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta-cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB), (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73, 51.64 and 54.05 per concentration decade with average recoveries of 99.92+/-1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta-CD respectively. Pyritinol also showed near Nernestian responses over the concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit-RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10 and 32.89 per concentration decade and average recoveries of 99.99+/-0.827, 100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD respectively. The sensors were used successfully for the determination of I and II in laboratory prepared mixtures with their degradation products, in pharmaceutical dosage forms and in plasma.